The lack of effective vaccines and therapeutic treatments for many viruses presents a heath concern of significant proportions. Host defenses against viruses require adaptive immune functions provided by both B cells and T cells, but the cellular and molecular processes that control the functions of these cells are incompletely understood. Although the persistence of viral antigens, the cytokine milieu in local microenvironments, the concentration and placement of immune cells in lymphoid and non-lymphoid organs, and the availability and type of costimulation can all dramatically affect the ultimate biological outcome of an immune response to virus infection or vaccination, it is unclear how these factors are controlled or how viruses manipulate each of these factors to evade or subvert immunity. These basic knowledge gaps limit our ability to rationally design new vaccines and to develop interventions to treat virus-mediated diseases. Therefore the overall goal of this U19 Program is to determine how various types of virus infections (chronic systemic, acute-systemic and acute-mucosal) affect the factors described above and lead to specific types of immune responses. In order to meet this goal, five labs with complementary expertise in human and mouse anti-viral immunology will work collaboratively to some of the key unresolved issues in anti-viral immunity. The major objectives of Core A are to provide administrative oversight and support for the program as a whole and for each of the individual projects, to provide biostatistics support for all the projects, to organize the external advisor visits, to organize yearly trips to the U19 conference and to organize monthly phone conferences and yearly face-to-face meetings of the investigators in each of the projects